In mammals the development of host protection against pathogens requires a selective host immune response that involves the mobilization of the humoral and/or cellular mediated immune responses. Several factors adversely affect the body's protective response capability by causing prolonged immune-suppression or "down-regulation" of the immune system associated with immune suppression is decreased resistance to infection. Immune-suppression provides an opportunity for pathogens to grow in the host. It does not matter what causes the primary insult to immunity. The resulting inability to muster the appropriate defensive response has the damaging effect of allowing organisms to grow and multiply in the host. Among the causes of immune-suppression are viral, bacterial, fungal, and parasitic infections, chemotherapy, irradiation, severe stress, and steroid therapy.
It has long been known some of the steroids of adrenocortical origin at pharmacologically appropriate doses cause patients to exhibit increased incidence of infectious disease. A. S. Fauci, Immunolo. Rev. 65, 133-155 (1982); and J. E. Parillo and A. S. Fauci, Annual Review of Pharmacology and Toxicology 19, 179-201 (1979).
Dehydroepiandrosterone, also known as 3-.beta.-hydroxyandrost-5-en-17-one or dehydroiso-androsterone (referred to hereinafter as DHEA), is a 17-ketosteroid which is quantitatively one of the major adrenocortical steroid hormones found in mammals. M. E. Windholz, The Merck Index, Ninth Edition (1976); K. Diem and C. Lentner, Geigy Scientific Tables (1975). Although DHEA appears to serve as an intermediary in gonadal steroid synthesis, the primary physiological function of DHEA has not been fully understood. It has been known, however, that levels of this hormone begin to decline in the second decade of life, reaching 5% of the original level in the elderly.
Clinically, DHEA has been used systemically and/or topically for treating patients suffering from psoriasis, gout, and hyperlipemia. It has also been administered to post-coronary patients. (W. Regelson et al., New York Academy of Sciences 518, 260-273 (1988).) In mammals DHEA has been shown to have anti-obesity and anticarcinogenic effects.
DHEA has been used clinically in Europe in conjunction with estrogen as an agent to reverse menopausal symptoms and also has been used in the treatment of manic depression, schizophrenia, and Alzheimer's disease. DHEA has also been used clinically at 40 mg/kg/day in the treatment of advanced cancer and multiple sclerosis. Regelson, supra. Mild androgenic effects are often associated with administration of DHEA. These side effects can be overcome by monitoring the dose and/or by using analogues.